Although cancer is the leading cause of morbidity and mortality in children beyond infancy, etiologic factors are not known, except in few cases. Clues from epidemiologic studies in adults and from animal data suggest that substances which could produce germinal mutations may also act to produce malignant transformation in somatic cells. We propose to investigate possible etiologic factors in childhood cancer, which could explain the uniform incidences of some cancers around the world (spontaneous fraction), the preponderance of multicentric or bilateral cases in some instances (germinal mutations), and the environmental factors causing both somatic and germinal mutations. By identifying individuals at high risk of childhood cancer we may be able to devise methods of prevention. The methods used will involve (1) The Greater Delaware Valley Pediatric Tumor Registry (GDVPTR), a population based registry, in order to monitor the incidence of childhood cancer in a 31-county region and to determine tumor-specific incidence rates especially comparing the incidence of multicentric cases with expectations. (2) A case-control study to test hypotheses concerning important risk factors in the etiology of childhood cancer. This would include approximately 650 children with various malignant diseases and 1300 controls to investigate pre-natal, gestational, and post-natal exposures such as those known to be mutagens or carcinogens in animal systems and adults.